The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer

• Published in: Human pathology Vol. 80; pp. 219 - 230
• Main Authors: Fararjeh, Abdul-Fattah Salah, Tu, Shih-Hsin, Chen, Li-Ching, Liu, Yun-Ru, Lin, Yen-Kuang, Chang, Hang-Lung, Chang, Hui-Wen, Wu, Chih-Hsiung, Hwang-Verslues, Wendy W., Ho, Yuan-Soon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018; Elsevier Limited
• Subjects: Breast cancer; Cancer therapies; Estrogen receptor; GATA3; Immunoglobulins; Medical prognosis; Metastasis; Multivariate analysis; Overall survival; Patients; Prognostic factor; Proteins; Studies; United States > US; Prognostic factor; Estrogen receptor; Breast cancer; GATA3; Overall survival
• ISSN: 0046-8177; 1532-8392; 1532-8392
• DOI: 10.1016/j.humpath.2018.06.004

The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor–positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P < .001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P = .018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P < .001) with higher H-score in Luminal A patients (P = .012). Kaplan–Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. •GATA3 is an ER+ breast tumor marker.•GATA3 is an effective prognosis marker for Luminal A breast cancer.•Relatively high GATA3 predicts a better overall survival for lower tumor grade and ER+.•GATA3 regulates ERα and BCL-2, which are considered as Luminal A markers.